Molecular docking studies of N-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives as potential modulators of glutamate receptors

Authors

DOI:

https://doi.org/10.3897/rrpharmacology.6.52026

Abstract

Introduction: The virtual target-oriented screening is a necessary stage of modern drug-design. In the present study, the affinity of pyridazine derivatives for the most promising antiparkinsonian biotargets – I–III groups of metabotropic and ionotropic NMDA-glutamate receptors – was evaluated.

Materials and methods: Docking of the studied ligands to the active sites of biotargets – mGluR5, mGluR3, mGluR8, NMDA GluN2B – was performed using AutoDockVina. Base of the preparation of ligands and proteins – AutoDock­Tools-1.5.6. A Discovery Studio Visualizer 2017/R2 was used to visualize the interpretation of the results.

Results and discussion: A high degree of the affinity is predicted for group III of the metabotropic mGlu8 receptors – binding energy from -5.0 to -8.7 kcal/mol, compared to -6.1 kcal/mol of that of the reference drug (L-AP4), as well as for the ionotropic NMDA GluN2B receptors –binding energy from -8.7 to -11.6 kcal/mol, compared to -11.3 kcal/mol of that of ifenprodil.

Conclusion: The prospects of the searching for glutamate receptor modulators in a number of n-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives are proved. Some aspects of the structure-affinity relationship are discussed.

Keywords:

pyridazine, antiparkinson agents, docking, mGluR, NMDA

Author Contribution

Natalia V. Avdeeva, National University of Pharmacy

PhD in Medical Sciences, Associate Professor.

Hanna I. Severina, National University of Pharmacy

PhD in Pharmaceutical Sciences, Associate Professor of the Department of Pharmaceutical Chemistry.

Victoriya A. Georgiyants, V.N.Karazin Kharkiv National University

Doctor of Sciences (Pharmacy), Professor, Head of the Department of Pharmaceutical Chemistry.

Sergiy M. Kovalenko, Kursk State Medical University

Doctor of Sciences (Chemstry), Professor.

Artem I. Yarcev, Kursk State Medical University

6-year student, Faculty of Medicine.

Svetlana N. Prohoda, Kursk State Medical University

Medical doctor.

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Published

30-03-2020

How to Cite

Avdeeva NV, Severina HI, Georgiyants VA, Kovalenko SM, Yarcev AI, Prohoda SN (2020) Molecular docking studies of N-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives as potential modulators of glutamate receptors. Research Results in Pharmacology 6(1): 69–82. https://doi.org/10.3897/rrpharmacology.6.52026

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Section

Review article

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